Over the past few years, it has become clear that exposure to mold in water-damaged buildings can have severe adverse effects on human health. As a neuroscientist, I am particularly interested in the effects of mold exposure on neural and cognitive function. Yet despite mounting evidence that mold exposure causes increased anxiety, depression, chronic fatigue, pain, and cognitive problems, no animal research has been published examining how mold exposure causes these problems. The goal of this pilot project is to begin to establish a mouse model to determine how mold exposure affects brain function and behavior. Mold exposure activates an innate immune response. My basic hypothesis is that Innate immune activation caused by mold, like that caused by bacterial infection, initiates "sickness behavior." Many of the problems, including the learning deficits, shown by mold-exposed patients are concordant with the effects of sickness behavior. Mold-exposed patients have difficulties with the types of learning tasks mediated by the hippocampus. Three experiments will be run to determine the effects of different types of mold exposure on sickness behavior: the ability to do a number of hippocampal-dependent cognitive tasks, microglial activation, cytokine and growth factor immunoreactivity, apoptosis and neurogenesis in the hippocampus of C57BI/6 mice. The relationships between these variables will be determined. Determination of the underlying physiological processes will allow the development of more rational therapies to treat mold- induced cognitive problems and possibly those caused by other disease processes which activate the same immune, endocrine, and neural mechanisms. [unreadable] [unreadable] This pilot project serves as a major change in research focus for me. It is structured to provide the mentoring and training I need to master the techniques needed for this research, complete the experiments, publish them in a timely fashion, and secure SC1 or equivalent funding to continue this line of research. [unreadable] [unreadable] [unreadable]